Research Finds Connection Between Increased Hepatitis E Virus Seroprevalence and Chronic Inflammatory Demyelinating Polyneuropathy

A newly published European study in Scientific Reports demonstrated that significantly more patients with chronic inflammatory demyelinating polyneuropathy (CIDP) tested positive for anti-hepatitis E virus (HEV)-immunoglobulin G (IgG) compared with patients with non-CIPD peripheral neuropathy or those with myasthenia gravis (MG). These results suggest that the development of CIDP may be triggered by HEV exposure in an HEV genotype 3 endemic region.¹

Among the patients recruited for the study, 102 patients had CIDP, 102 were age- and sex-matched blood donors, 61 had peripheral neuropathy (non-CIDP patients), and 26 had MG. Among those with CIDP, 64% tested positive for anti-HEV IgG (n = 65) and 1% tested positive for anti-HEV IgM (n = 1). Researchers noted that there were no other patients identified that tested positive for anti-HEV IgM.

“Several studies have demonstrated an association between HEV infection and neurological conditions like [hyponatremia] or [Guillain-Barré syndrome], which are considered causative parainfectious autoimmune phenomena. Our study clearly shows that patients with CIDP, another rare neurological inflammatory disease of the peripheral nervous system, have a significantly increased anti-HEV IgG seroprevalence” lead author Sven Pischke, MD, PhD, associate professor in the department of medicine at University Medical Centre Hamburg-Eppendorf in Germany, and colleagues wrote.¹

In this study, investigators enrolled participants from 2 German cities: Hamburg and Hannover. In Hamburg, patients were recruited between May and September 2021. Researchers tested serum samples from these patients for anti-HEV IgG and IgM and if positive, results were confirmed with an immunoblot.² To validate these findings, additional patients with CIDP and patients with non-CIDP from Hannover were retrospectively analyzed for anti-HEV antibodies and HEV viremia. All patients with CIDP were also compared with an age- and sex-matched control group of blood donors.

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In the subgroup of patients who had an initial diagnosis of CIDP and were not treated previously IVIG treatment (n = 54), researchers reported that 56% (n = 30) of these patients tested positive for anti-HEV IgG. Investigators also noted significantly lower anti-HEV rates among the blood donors (28%), patients with non-CIDP peripheral neuropathy (20%), and patients with MG (12%). Notably, authors observed that none of the participants tested positive for HEV viremia, and that 61 patients with CIDP tested negative in the cerebrospinal fluid.

“A detailed examination of a subgroup of patients with an initial CIDP diagnosis was performed in the current study to exclude the influence of these factors. This analysis revealed a significant increase in anti-HEV IgG positivity in this cohort, which had never received IVIG,” Pischke et al noted.¹ “In nearly 100% of these patients, IgG positivity was confirmed by a blot test. Therefore, prior exposure to HEV, rather than IVIG-mediated anti-HEV IgG antibodies, is indeed the cause of the heightened anti-HEV seropositivity in CIDP patients.”

Despite the significance of the results observed in the CIDP cohort, researchers recommended larger multicenter studies for further validation. Investigators also noted that additional research should delve into immunological aspects since the current study results were based solely on serology. Authors reported that this study did not observe distinct clinical or serological features in CIDP with prior HEV exposure, highlighting the need for larger, more diverse cohorts. Additionally, researchers suggested that future studies should extend to other neurological diseases and IVIG-treated conditions.

“Initially, it was hypothesized that neurological disorders might stem from viral replication in neuronal cells. However, CIDP, typically considered autoimmune, challenges this view. Traditionally, autoimmunity was thought to target myelin sheaths, but our findings suggest HEVs may play a direct role, possibly initiating misdirected immune responses,” Pischke et al noted.¹

REFERENCES
1. Pischke S, Kjasimov A, Skripuletz T, et al. Serological indication of chronic inflammatory demyelinating polyneuropathy as an extrahepatic manifestation of hepatitis E virus infection. Sci Rep. 2024;14(1):19244. Published 2024 Aug 20. doi:10.1038/s41598-024-70104-3
2. Kraef C, Schlein C, Hiller J, et al. Course of HEV viremia and anti-HEV IgM/IgG response in asymptomatic blood donors. J Clin Virol. 2018;105:26-30. doi:10.1016/j.jcv.2018.05.013